CAREER: Linking Mechanical Forces and Energy Flow in Collective Cell Migration

This Faculty Early Career Development Program (CAREER) award supports research to apply novel biomechanics and engineering methods to determine how mechanical forces and cellular energy constraints work together to guide the motion of cells. Cells often move as groups rather than as single cells. This process is important in tissue formation, wound repair, and disease progression, such as cancer invasion and tissue fibrosis. Yet it remains difficult to determine how cells coordinate movement in three-dimensional environments that more closely resemble living tissues. In these settings, cells must both transmit forces to one another and use energy to sustain motion. Current methods do not allow these processes to be studied well within realistic tissue environments. The knowledge and tools developed through this research project will provide a foundation for future studies of tissue growth, repair, and diseases such as cancer. The project will also contribute to broader national interests in biotechnology by advancing methods to study coordinated cell behavior in realistic tissue environments and help advance the national health. In addition, it will connect research with education through hands-on learning, outreach activities, and broad sharing of experimental and analytical tools for students and researchers. In this way, the project will help establish a sustained research and training effort in biomechanics and mechanobiology. This CAREER award supports research that focuses on understanding how intercellular forces and cellular energy constraints regulate collective migration in three-dimensional environments. The research will use a recently developed method for mapping intercellular stresses in three-dimensional cell collectives, together with bioenergetic measurements, engineered tissue models, and deep learning-based image analysis, to determine how force patterns and energy constraints shape coordinated movements. The objectives are to determine how intercellular forces, especially compressive stresses, direct collective migration; to define the active mechanical and energetic roles of follower cells; and to determine how energy gradients and physical confinement guide directional flow and spatial organization during collective migration. The research will be closely integrated with education and outreach, using the same toolset and experimental framework to support research training, hands-on course activities, outreach programs, and practical workshops for researchers. The project will advance fundamental work in biomechanics and mechanobiology by establishing a force-energy framework for collective migration in tissues, while making the new enabling tools more broadly accessible. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria. NSF Award ID: 2543245 | Program: 01002627DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Jian Zhang | Institution: University of Arkansas, FAYETTEVILLE, AR | Award Amount: $504,665 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2543245 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2543245.html